PDF(Pubmed)
Abstract：
Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline \'Diagnostics and therapy of myasthenic syndromes\' has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity.
摘要：
重症肌无力(MG),兰伯特-伊顿肌无力综合征（LEMS），先天性肌无力综合征（CMS）代表病因上异质性的（非常）罕见的慢性疾病组。MG和LEMS有自身免疫介导的病因，而CMS是遗传性疾病。由于神经肌肉传递障碍引起的(应变依赖性)肌肉无力是常见特征。广义MG需要考虑近年来巨大治疗发展的日益差异化的治疗策略。包括最新的治疗建议，德国神经学会在跨学科专家小组的帮助下,对可用的德语指南“肌无力综合征的诊断和治疗”进行了全面更新.本文是对更新和部分新开发的治疗指南的改编翻译。它将快速实现肌无力患者的完全疾病控制定义为中心治疗目标。使用标准疗法，以及现代免疫疗法，接受考虑自身抗体状态和疾病活动性的分阶段方案。随着现代的到来，速效免疫调节剂,疾病活动性评估已成为关键，需要对临床过程进行评估，包括严重程度和所需的治疗。应用MG特异性评分和分类，如重症肌无力日常生活活动，定量重症肌无力,和美国重症肌无力基金会允许区分轻度/中度和（高度）活跃（包括难治性）疾病。治疗决定必须考虑年龄，胸腺病理学,抗体状态，和疾病活动。糖皮质激素和经典的免疫抑制剂（主要是硫唑嘌呤）是治疗轻度/中度至（高度）活性的全身性MG/年轻MG和眼部MG的基本免疫治疗剂。胸腺切除术可用于治疗胸腺瘤相关MG和乙酰胆碱受体抗体（AChR-Ab）阳性的全身性MG。在(高度)活性广义MG中，对于AChR-Ab阳性状态推荐补体抑制剂(目前为依库珠单抗和ravulizumab)或新生儿Fc受体调节剂(目前为efgartigimod),对于肌肉特异性受体酪氨酸激酶(MuSK)-Ab阳性状态推荐为利妥昔单抗.肌无力危象的特殊治疗需要血浆置换，免疫吸附，或IVIG。眼的具体方面，少年,和先天性肌无力突出。该指南将根据其他免疫调节剂和生物标志物的新研究结果进一步开发，以帮助准确测量疾病活动。
